Can Stem Cells Fix a Weakened Pelvic Floor?

In England in 1670, a peasant woman named Faith Raworth took a sharp knife and cut off a melon-sized lump of flesh protruding from her vagina. She survived the subsequent bleeding in what was probably the first successful do-it-yourself surgery for pelvic organ prolapse. However, she suffered urinary incontinence for the remainder of her life, according to the case studies of 17th-century physician Dr. Percival Willoughby, who was, as he expressed it, “actively engaged in the practice of Midwifery.”

Dr. Willoughby is one among many who has reported the bulging of parts of the uterus into and through the vagina during the past 2,000 years, says Hadassah gynecologist Dr. David Shveiky, director of Female Pelvic Medicine and Reconstructive Surgery, a division within the Hadassah-Hebrew University Medical Center’s Obstetrics and Gynecology Department. “As women age, their pelvic floor muscles, ligaments and connective tissue—together comprising a kind of hammock across the pelvic floor that holds the uterus and bladder in place—begin to weaken, allowing these organs to droop into the vagina.”

Never rare, pelvic organ prolapse now has reached epidemic proportions, with a massive 50 percent increase predicted by 2050. “Global populations are graying, and prolapse is a condition that increases with age,” says Dr. Shveiky. “Although peak incidence is between the ages of 70 and 79, it can occur far earlier. Most of my patients are in their 50s, though I’ve operated on women in their 30s, too.”

Today, one in two women will experience pelvic-floor complaints, he says, which can mean constant pressure in the vagina or groin, lower back pain, difficulty urinating or urine leakage, constipation and painful sex. Up to one in five will be treated surgically—some 300,000 procedures a year in the United States alone—according to the National Institutes of Health, consuming hundreds of millions of health care dollars.

For some prolapse patients, reconstructive surgery is the only option. “Whether we operate through the vagina or the abdomen, in open, robotic or laparoscopic surgery, we aim to stitch the organs back in place,” explains Dr. Shveiky. “But results are sometimes disappointing and prolapse recurs in more than 30 percent of patients.” In addition to the risks of infection, bleeding and scarring, the weakened connective tissue often takes poorly to repair, with further tearing or urinary leakage.

One solution is synthetic grafting, a surgical mesh long used for abdominal hernias and urinary stress incontinence. A thin netting made from polypropylene, the material used for plastic chairs and bottles, surgical mesh was initially hailed as the best solution in prolapse surgery. Increasingly, however, the mesh has been associated with pain, bleeding and infection. With tens of thousands of lawsuits filed against it worldwide, the United States Food and Drug Administration issued a public health notification in 2011, warning of the mesh’s “serious complications.” It advises using the mesh with caution, fully informing patients of its risks and limiting it to women with recurrent prolapse whose connective tissue has demonstrably failed.

“Despite its complications, a vaginal mesh remains the main alternative where repair using natural tissue isn’t good enough,” says Dr. Shveiky. “Clearly, there’s urgent need to find other ways of augmenting tissue strength.”

One such option, for milder cases, is a type of vaginal anchor that was developed by Israeli startup Escala Medical and for which Dr. Shveiky performed the preclinical studies. Nonsurgical and incision free, it is introduced by applicator to support the weakened vaginal wall. Now at the validation stage, it is awaiting FDA approval and could be on the market within a year.

Another treatment in development for pelvic organ prolapse is stem cells and tissue engineering—a field introduced to Dr. Shveiky by Dr. Benjamin Reubinoff, director of the Sidney and Judy Swartz Human Embryonic Stem Cell Research Center in Hadassah’s Goldyne Savad Institute of Gene Therapy and current head of obstetrics and gynecology at Hadassah. An internationally known stem cell researcher, Dr. Reubinoff believes “stem cell therapy can replace diseased or malfunctioning cells with healthy tissue tailor-made from flexible young stem cells and thus lead to effective treatment for pelvic organ dysfunction.”

Dr. Shveiky, along with Dr. Reubinoff and postdoctoral candidate Ofra Ben Menachem-Zidon, has established a laboratory to investigate how stem cells work in women’s health. In animal models, the team has shown that old and young animals heal differently—that is, age influences the way the body repairs vaginal wounds.

“We took our vaginal wound-healing model and injected vaginal stem cells from the animal models intravenously, immediately after tissue injury,” says Ben Menachem-Zidon, graduate of a fellowship in stem cell research at the University of Cambridge in England. “The results showed we are on the right track. The injected stem cells went directly to the area of injury, where they began building the blood vessels and other structures associated with wound healing, and they restored the slower healing associated with age to the level seen in younger animals.”

The day is coming closer, Dr. Shveiky believes, “when we’ll be able to extract stem cells from a woman’s own reserve, prepare them as vaginal cells and return them to her to rejuvenate her pelvic tissues and heal pelvic organ prolapse. A natural process, devoid of synthetic or foreign materials, we see it as a safe and effective answer to a debilitating and distressing condition that causes so many women so much anguish.

“Gynecology is about both medical and surgical treatment of patients of all ages,” Dr. Shveiky adds, “and it embraces a wide spectrum of problems from high-risk pregnancy to oncology.” While the field had long been of interest to Dr. Shveiky, urogynecology and pelvic surgery had initially seemed to him mechanical and unglamorous. However, that changed as he made his way from medical school to internship to residency, all at Hadassah.

Dr. Shveiky spent a three-year fellowship in Washington, D.C., at the MedStar Washington Hospital Center and Georgetown University under leading pelvic reconstructive surgeons, training in vaginal, robotic and laparoscopic pelvic surgery. He returned to Hadassah in 2010 as Israel’s first fellowship-trained robotic pelvic reconstructive surgeon. With the encouragement of Dr. Neri Laufer, then head of Hadassah’s Obstetrics and Gynecology Department, Dr. Shveiky set up the Female Pelvic Medicine and Reconstructive Surgery division. “We operate on more than 230 women a year and receive around 1,200 clinic visits,” he says.

During internship and residency, “I was increasingly struck by the bias in gynecological practice, especially in Israel,” he recalls. “Its focus is fertility—getting pregnant, the best prenatal testing for the best pregnancies that produce the best children. I felt we lost sight of the mothers once the umbilical cord was cut, even though the consequences of pregnancy, labor and delivery can be lifelong.”

What, for example, causes pelvic organ prolapse? Why is it at epidemic level and rising? Is it, as commonly believed, linked with the plummeting estrogen of menopause? Do women need estrogen to maintain the integrity of their connective tissue, as they do for the integrity of their skin?

Dr. Shveiky was able to provide answers to some of these questions when, in 2010, he was given access as a project chairman to the results of the Women’s Health Initiative—a groundbreaking 15-year study of 161,808 women aged 50 to 75 initiated by the NIH. Launched in 1991 to examine all aspects of women’s health, one of its best-known findings is the link between hormone replacement therapy and breast cancer.

The study also amassed detailed information about some 10,000 women who have undergone surgical menopause via removal of the uterus, says Dr. Shveiky. “We tracked exposure to the so-called ‘protective function’ of estrogen by comparing incidence of pelvic organ prolapse in women who have had their estrogen-producing ovaries removed at hysterectomy with those whose ovaries were left in place. We factored in data about which of these women received estrogen therapy and for how long.”

Dr. Shveiky’s research proved revolutionary, overturning long-held medical belief about estrogen’s protective function. Published in the journal Menopause two years ago, it showed that estrogen provides no protection at all. Dr. Shveiky identified prolapse risk factors as older age, higher parity—the more and bigger babies a woman has, the greater her risk—and obesity, which doubles the risk. “Jerusalem, with its large and fertile ultra-Orthodox Jewish and Arab populations, has many such women,” he says. “One on whom I recently operated was a mother to 17!”

One of his patients, a 57-year-old mother of eight who asked not to be identified to protect her privacy, recalls that “it took me the longest time to get myself to a doctor. I kept telling myself there was nothing wrong,” she says. “Even after it was clear something was very wrong, I just hoped it would fix itself and go away. I didn’t go for medical help until I couldn’t walk or even sit without pain.”

These women, Dr. Shveiky notes, are often the family caregivers—tending to husbands, children and grandchildren. “They’re too busy to seek medical help for a condition that is not life-threatening,” he says, “and they’re uncomfortable talking about intimate body parts, but this doesn’t mean they don’t suffer. They live with a vaginal protrusion, sized anything from an egg to a melon.

“Beyond the many physical symptoms, they feel shame,” he continues. “Pelvic organ prolapse is a health problem, but it’s also about human dignity and physical, emotional and sexual quality of life.”

Wendy Elliman is a British-born science writer who has lived in Israel for more than four decades.

This is wonderful news. Please, please, please look at how stem cell research applies to women with levator avulsion. When the levator rips from the bone in childbirth, prolapse is just one complication. Since more and more AMA mothers birth, the increase of avulsion is rising (see the work of Dietz for example) We desperately need your help!

I have chronic pain in my rectum. Debilitating at times. Nothing helps. 3 proctologist call it a Levator ani problem.
I suffer with a lot of pain. I am 71 yrs old in excellent health otherwise.
I live in Atlanta.. suggest anyone here for stem cell help. I had stem cells in a tendon at Emory yrs ago , it was 100% successful .
Thanks ,

I am 72 yr old woman who suffers from prolapse where very often protrudes outside my vagina.
I had a partial hysterectomy around age 42. My uterus has been removed but still have my ovaries. I did not take any hormone replacement before after or during menopause or after my partial hysterectomy.
I have been against the mesh from the onset and reluctant to do so holding out for a better cure.
I am at stage 4 and am very interested in the stem cell procedure. Please let me know as studying go forward and when it will be available for Dr’s to move forward on helping woman world wide a better choice and quality of life.
CmGopalan
Bluffton SC
USA

I had a rectocel fixed surgically at age 67 and now at 73 have a cystocele. I don’t want to go through the pain and suffering of that operation again! I am doing kegel exercises and am interested in stem cell therapy. I took prempro for ten years and now use Premarin cream, but it didn’t prevent this.

I would be more than happy to participate in any trials for this treatment! This is now my only hope! Ive suffered for 14 years with this life destroying condition and I’m only 35. Please hurry with your research, a new approach is desperately needed!